POS0896 CONFOUNDING BY INDICATION IN OBSERVATIONAL STUDIES INVESTIGATING GLUCOCORTICOID-ASSOCIATED ADVERSE EVENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW

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Background: Patients with rheumatoid arthritis (RA) who have more severe and active disease are more likely to experience adverse events (AEs; e.g., cardiovascular events or fractures) and to be prescribed glucocorticoids (GCs). To reliably assess the relationship between GC use and AEs, observational studies need to adjust for disease activity or markers of systemic inflammation. Objectives: To assess use of statistical strategies to adjust for disease activity or markers of systemic inflammation in addressing potential confounding by indication in observational studies of RA investigating GC-related AEs. Methods: We conducted a protocolized (https://dx.doi.org/10.17504/protocols.io.bp2l6x955lqe/v1) systematic literature review. MEDLINE was searched for observational studies in patients with RA that investigated the association between GCs and AEs of interest (death, bone-related, cardiovascular, endocrinological, infectious, psychiatric, ophthalmological) published after 2007. GCs had to be mentioned in the study abstract. We calculated the proportion of studies that statistically adjusted for validated disease activity scores (e.g., RAPID3) and/or systemic inflammation (e.g., serum CRP levels) and/or both (e.g., both RAPID3 and CRP or combined scores such as DAS28-CRP). Joanna Briggs Institute's critical appraisal checklists (https://jbi.global/critical-appraisal-tools) were used for quality appraisal. Analyses were further stratified by study characteristics (year of publication [cut-off: median], study type, type of AE, critical appraisal checklist score percentages [cut-off: median], and 2022 Journal Impact Factor® [cut-off: 10]). Statistical comparisons were made using Chi-squared tests (with Yates' continuity correction). Results: Out of 609 initial search results, 47 observational (mostly cohort) studies were finally included (Table 1). Most studies had a cohort design, were from North America or Europe, and assessed oral GCs. The most commonly investigated AEs were bone-related, such as bone mineral density or fractures, followed by cardiovascular and infectious AEs. Almost one third of all included studies was published in either Annals of the Rheumatic Diseases or Rheumatology (Oxford ). Most studies (57%) did not adjust for either validated disease activity scores or markers of systemic inflammation, regardless of study characteristics. Even in the subsets of studies that were published in a journal with a Journal Impact Factor® of ≥10 or that had critical appraisal checklist score percentages of ≥90%, the majority of studies did not statistically adjust for disease activity or markers of inflammation (Figure 1). Studies published after 2018 were not more likely to adjust compared to earlier studies (adjustment for disease activity: 35% vs. 31% [p = 0.99], respectively; adjustment for inflammation: 40% vs. 38% [p = 0.99], respectively). Conclusion: Confounding by indication is likely present in most observational studies investigating the relationship between GC use and AEs. Even studies published in "high-ranking" scientific journals did not regularly adjust for disease activity or markers of systemic inflammation. Despite not taking the possibility of confounding by indication into account, observational studies may achieve relatively high quality appraisal scores using a commonly accepted critical study appraisal tool. REFERENCES: NIL . Acknowledgements: NIL . Disclosure of Interests: Andriko Palmowski Novartis, unrelated to this manuscript, Anne Pankow: None declared, Judith Oldenkott: None declared, Henriette Käding: None declared, Arnd Kleyer: None declared, Eric Matteson Boehringer Ingelheim GmBH, Horizon Therapeutics, Amgen and Crystalys Therapeutics, all unrelated to this work, Edgar Wiebe: None declared, Zhivana Boyadzhieva: None declared, Anne Elisabeth Beenken: None declared, Frank Buttgereit AbbVie, Pfizer, Gruenenthal, and Horizon Therapeutics, all unrelated to this manuscript. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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